Amino acid preference against beta sheet through allowing backbone hydration enabled by the presence of cation (1610.00375v1)

Abstract: It is known that steric blocking by peptide sidechains of hydrogen bonding, HB, between water and peptide groups, PGs, in beta sheets accords with an amino acid intrinsic beta sheet preference. The present observations with Quantum Molecular Dynamics, QMD, simulation with quantum mechanical treatment of every water molecule solvating a beta sheet that would be transient in nature suggest that this steric blocking is not applicable in a hydrophobic region unless a cation is present, so that the amino acid beta sheet preference due to this steric blocking is only effective in the presence of a cation. We observed backbone hydration in a polyalanine and to a lesser extent polyvaline alpha helix without a cation being present, but a cation could increase the strength of these HBs. Parallel beta sheets have a greater tendency than antiparallel beta sheets of equivalent small size to retain regular structure in solvated QMD, and a 4 strand 4 inter-PG HB chain parallel beta sheet was used. Stability was reinforced by one surface being polyvaline, which buttressed the opposite surface which was used for experimentation. A single Ca2+ ion was used for investigation of individual binding events rather than bulk properties. No direct binding between Ca2+ and the PG oxygen was observed in these simulations, but perhaps it occurs at longer time scales as the transient beta sheet unfolds. When linear scaling QMD methods that are accurate for peptide resonance, Resonance-Assisted Hydrogen Bonding and the properties of water become available, more extensive experiments having multiple ions of multiple types could be performed at acceptable computational cost. It important that such investigations be performed on protein secondary structures rather than model amides so that sidechain limitation of backbone hydration and hence intrinsic amino acid propensity is captured.